ART Medications

Several medications are used in a typical IVF cycle. These
medicines belong to several categories and each are an important part of a
stimulated cycle. The types and amount of medications used vary according to
the medication protocol prescribed by your physician.

GnRH Agonists

Gonadotropin releasing hormone (GnRH) is a hormone produced
in the brain that indirectly stimulates ovarian function. Agonists of GnRH are
synthetic forms of this hormone which do not directly induce follicle
development or ovulation but which have become very important in ART therapy.

There are several advantages to using GnRH agonists:

They make
ovarian stimulation easier to regulate, since the patient's own hormone
production is suppressed.

Patients
who are treated with GnRH agonists tend to produce a greater proportion of
mature oocytes than patients who do not receive them.

GnRH
agonists markedly decrease the risk of cycle cancellation for most
patients. Prior to their use, 20-50 percent of IVF-ET cycles were canceled
because patients would have a premature LH surge with spontaneous
ovulation. Using GnRH agonists, the risk of cycle cancellation is less
than 5 percent.

Ovarian
function can be suspended with GnRH agonists for variable periods of time
if necessary, which allows for flexibility in cycle scheduling.

Mechanism Of Action

Agonists of GnRH (such as Lupron®) initially stimulate the
pituitary gland to release all the stored gonadotropins (LH and FSH -the
hormones that normally stimulate ovarian function). Over the course of a week
to 10 days, GnRH analogs suppress the production of any new LH and FSH. This
effect appears to prevent the ovaries from receiving mixed signals from the
patient's own LH and FSH and from the medications that are administered to
stimulate follicle development. The result for many patients is a more
synchronized development of mature oocytes.

Dosage and Monitoring

The GnRH agonist used most commonly is leuprolide acetate
(Lupron®). Lupron® is not FDA approved for use in IVF treatment but has been
used successfully in IVF for 20 years. Lupron® must be injected to be active.
In ART therapy, a formulation of Lupron® is used, which can be injected just
under the skin, in a manner similar to insulin injections for diabetes therapy.

The usual dosage of Lupron® is 0.1 or 0.2 cc daily as a
single injection. Menstruation usually occurs four to 10 days later. During the
time of actual ovarian stimulation, the dosage of Lupron® is halved (e.g., 0.1
cc to 0.05 cc daily). Lupron is usually administered until the day of hCG
administration. Some patients, because of their history or condition, are
treated with a different dosage or schedule of Lupron®.

In some protocols, a GnRH analog can be used to trigger
ovulation of mature follicles in place of human chorionic gonodpotropin. This
is usually reserved for patients with a risk of hyperstimulation.

Another GnRH analog used in ART therapy is nafarelin
acetate (Synarel®). Synarel® is administered as a nasal spray. The usual
starting dose is two sprays twice a day. The timing of administration is
identical to Lupron®. The dosage of Synarel® is usually halved (e.g., from two
sprays twice a day to one spray twice a day) when ovarian stimulation is begun.

GNRH Antagonists

Antagonists of GnRH are also available (Cetrotide® and
Antagon®). These are started later in the cycle than Lupron® and directly and
immediately inhibit FSH and LH production. Protocols that use these medications
may require fewer injections. Ultrasound measurements of follicular growth are
used to determine when to start these medicines.

Mechanism of Action

GnRH antagonists bind to the receptor for gonoadotropin
releasing hormone on the pituitary, preventing the natural luteinizing hormone
surge and ovulation. This is important to the success of an IVF cycle, when
premature ovulation could reduce the number of oocytes retrieved.

Gonadotropins

To increase likelihood of pregnancy through ART, multiple
oocytes must be produced. This is accomplished through the administration of
gonadotropins, hormonal medications that directly stimulate the ovaries.
Stimulation can be achieved with a variety of drug regimens. Gonadotropin
medications come in several forms; Repronex® and Menopur® are a combination of
FSH and LH. They replace a woman's own LH and FSH which are normally produced
by the pituitary gland. Bravelle®, Follistim® AQ Cartridge for use with
Follistim Pen®, Follistim® AQ Vial, Gonal-F®, and Gonal-F® RFF Pen are
preparations that contain only FSH. Follistim® AQ Cartridge for use with
Follistim Pen®, Follistim® AQ Vial, Gonal-F®, and Gonal-F® RFF Pen are
recombinant products which are made by genetically engineered cells. This
process ensures uniform purity and potency. Because the dose of hormones that
are used in ART is greater than what the body normally produces, the ovaries
typically develop more than one oocyte as occurs in a natural cycle.

Gonadotropins act directly on the ovary to stimulate the
growth of follicles (the structures in the ovaries which contain eggs).
Granulosa cells within the follicles grow and develop which cause the follicles
to enlarge and fill with follicular fluid. These developing follicles can be
counted and measured using transvaginal ultrasound. As the follicles grow, they
produce increasing amounts of estrogen, which can be measured with a laboratory
blood test. Some physicians prefer one formulation or another. Your doctor can
discuss this with you in more detail.

Dosage and Monitoring

Gonadotropins are packaged in vials containing 37.5, 75 or
150 International Units (IU). Follistim AQ Pens and Gonal-F RFF Pens are
packaged in pre-mixed injectable pens. Multi-dose vials of some medications are
also available. Dosage may vary depending on the patient's history. Patients
will then have regularly scheduled transvaginal ultrasound examinations and
serum estradiol tests. The dose of gonadotropins is then determined by the
result of the ultrasound and estradiol tests. Most women require between seven
to 10 days of gonadotropin therapy.

Bravelle®, and Repronex® are administered subcutaneously or
by intramuscular injection, usually into the muscles of the buttocks. Gonal-F,®
Follistim,® Follistim AQ Pens, and Gonal-F RFF Pens are administered
subcutaneously, like an insulin or allergy shot.

Human Chorionic Gonadotropin

Human chorionic gonadotropin (hCG) is an injectable
medication that is administered to complete oocyte maturation. The brand names
for hCG are Profasi®, Ovidrel®, Novarel®,and Pregnyl®.

Mechanism of Action

Human chorionic gonadotropin is structurally similar to the
LH that is produced by a woman's pituitary gland. It acts on the ovary in a
manner similar to a woman's own LH. Human chorionic gonadotropin, like LH,
stimulates the final maturation of the oocytes in the follicle. It also
stimulates progesterone production from the ovary after egg retrieval. This
progesterone is important to prepare the uterus for implantation of the embryo.

Dosage and Administration

Human chorionic gonadotropin can be administered several different
ways. The commonly administered dose is a single injection of 10,000 units.
Once hCG is administered, ovulation usually occurs in approximately 36 to 40
hours. Therefore oocyte retrieval is routinely scheduled at 34-36 hours after
hCG. This helps ensure maximal egg maturity, which is important for
fertilization and embryo development. Occasionally, several doses of 2,500
units (usually every three days) are administered after egg retrieval to
stimulate progesterone production. If your response to stimulation is
particularly exuberant, the dose of hCG can be reduced to 5,000 units in an
attempt to reduce the risk of ovarian hyperstimulation syndrome.

It typically takes 8-10 days for single injection of 10,000
units of hCG to be cleared from the blood stream. As hCG is the same hormone
that is produced by a developing pregnancy, patients should not have a blood or
urine pregnancy test sooner than 10 days following the hCG injection. If a
pregnancy test is performed earlier, it may measure the hCG that was given by
injection rather than measure hCG produced by a pregnancy.

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